Human chromosome 10Q24 contains a putative tumor suppressor gene whose inactivation is responsible for the development of prostate cancer. The overall goal of this research project is to isolate transcribed sequences in this chromosomal region to identify candidates for this tumor suppressor gene. Two approaches will be used in this study: terminal exon trapping and direct cDNA selection. Both approaches will be applied to large genomic fragments cloned in yeast artificial chromosomes (YACs). The feasibility of large scale terminal exon trapping and direct cDNA selection from megabase sized YACs will be studied. A transcriptional map integrated with genetic cytogenetic and physical maps in the region will be constructed. This integrated map will be especially valuable for new disease gene identification in the future. PROPOSED COMMERCIAL APPLICATION: A gene for prostate cancer will have immense potential in diagnostics and therapeutics because of the magnitude of the disease in the western population. Exons and cDNAs isolated in this study will be developed into new DNA markers which can be marketed for use in genetic and physical mapping of the chromosome region, in mapping chromosome losses and LOH in tumors, and for DNA diagnosis of genetic diseases in the vicinity.